Bacteriophage may be produced using fermentation processes, in which liquid fermentation media, bacterial hosts, and bacteriophage are mixed with one another and incubated. Liquid lysate mixtures that include bacterial debris, fermentation media and an increased concentration bacteriophage result from such fermentation processes. In producing bacteriophage, the nature of the lysate and the interaction with the lysed host must be considered. Bacteriophage thrive within the fermentation environment, and typically continue to exist within that lysate for extended periods of time (with limited exceptions). If the bacteriophage is removed from the liquid lysate, or the environment is changed slightly, the viability of the bacteriophage could be compromised.
Additionally, liquids, such as water, promote the desired random interaction between bacteriophage and the targeted bacterial host. Accordingly, bacteriophage is typically applied in liquid form to substrates (e.g., plants, meats, etc.) that may be contaminated or infected with specific target bacteria.
As such, typically, liquid lysate solutions that result from bacteriophage fermentation processes are merely clarified to produce a final bacteriophage product, which is then shipped without further modification.
There are, however, situations where it would be more desirable to supply a dry bacteriophage product or a more compact (e.g., concentrated, etc.) bacteriophage product. An example of such a situation is when a host bacteria excretes a particular enzyme, protease, toxin, or other by-product that may harm the bacteriophage over time; e.g., by breaking down protein (which are the building blocks of bacteriophage), leading to the eventual demise of bacteriophage that remains within the liquid lysate solution (clarified or not). This breakdown occurs over time, even after the bacterial hosts have been killed by the bacteriophage, and can occur in as little as a few hours or as long as many days or even weeks. As a result, the production of liquid bacteriophage products has been limited to “well-behaved” bacterial hosts (those which do not excrete by-products that could harm the bacteriophage), which may limit the types or concentrations of certain types of bacteriophage that can be effectively produced on an industrial scale.
While various attempts have been made to produce dry bacteriophage products, including lyophilization (i.e., freeze-drying) and spray drying processes, the susceptibility of bacteriophage particles to the conditions (e.g., temperatures, shear forces, etc.) of such processes have rendered these attempts largely unsuccessful, “killing” or otherwise diminishing the virulence of the vast majority of the bacteriophage particles. In fact, conventional spray dry processes typically result in products with at least a five log (105) to eight log (108) reduction in bacteriophage efficacy, representing a reduction in the effectiveness of the final product, compared to its pre-dried liquid form, of 99.999% to 99.999999%.
There are needs for bacteriophage and bacteriophage-containing compositions that are in dry (e.g., powder, granules, etc.) form, for methods for drying bacteriophage and bacteriophage-containing compositions, and for methods for using dry bacteriophage and dry compositions that include bacteriophage.